Total submissions: 8
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000059052 | SCV000329058 | pathogenic | not provided | 2021-03-16 | criteria provided, single submitter | clinical testing | Published functional studies demonstrate a reduction of transactivation activity compared to normal protein (Meloni et al., 2008); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 21295522, 30018023, 15511668, 28446514, 23000069, 12398240, 17289071, 18713028, 15751604, 11836330, 17675238, 15811934) |
Counsyl | RCV000409203 | SCV000485843 | likely pathogenic | Polyglandular autoimmune syndrome, type 1 | 2016-02-25 | criteria provided, single submitter | clinical testing | |
Invitae | RCV000409203 | SCV000827161 | pathogenic | Polyglandular autoimmune syndrome, type 1 | 2023-09-08 | criteria provided, single submitter | clinical testing | ClinVar contains an entry for this variant (Variation ID: 68218). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on AIRE protein function. Experimental studies have shown that this missense change affects AIRE function (PMID: 17675238). For these reasons, this variant has been classified as Pathogenic. This missense change has been observed in individuals with autosomal recessive autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) (PMID: 11836330, 15811934, 17289071, 21295522, 28446514). This variant is present in population databases (rs179363889, gnomAD 0.006%). This sequence change replaces proline, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 539 of the AIRE protein (p.Pro539Leu). |
Blueprint Genetics | RCV000059052 | SCV000927331 | pathogenic | not provided | 2017-07-10 | criteria provided, single submitter | clinical testing | |
Fulgent Genetics, |
RCV000409203 | SCV002797214 | pathogenic | Polyglandular autoimmune syndrome, type 1 | 2022-03-29 | criteria provided, single submitter | clinical testing | |
National Institute of Allergy and Infectious Diseases - |
RCV000409203 | SCV004036196 | pathogenic | Polyglandular autoimmune syndrome, type 1 | 2023-09-14 | criteria provided, single submitter | clinical testing | |
Center for Genomic Medicine, |
RCV000409203 | SCV004806859 | likely pathogenic | Polyglandular autoimmune syndrome, type 1 | 2024-03-26 | criteria provided, single submitter | clinical testing | |
Uni |
RCV000059052 | SCV000090573 | not provided | not provided | no assertion provided | not provided |